This minireview briefly surveys the complexity of regulations governing the bone metabolism. The impact of clinical studies devoted to osteoporosis is briefly summarized and the emphasis is put on the significance of experimental mouse models based on an extensive use of genetically modified animals. Despite possible arising drawbacks, the studies in mice are of prime importance for expanding our knowledge on bone metabolism. With respect to human physiology and medicine, one should be always aware of possib le limitations as the experimental results may not be, or may be only to some extent, transposed to humans. If applicable to humans, results obtained in mice provide new clues for assessing un foreseen treatment strategies for patients. A recent publication representing in our opinion the important breakthrough in the field of bone metabolism in mice is commented in detail. It provides an evidence that skeleton is endocrine organ that affects energy metabolism and osteocalcin, a protein specifically synthesized and secreted by osteoblasts, is a hormone involved. If confirmed by other groups and applicable to humans, this study provides the awaited connection of long duration between bone disorders on one hand and obesity and diabetes on the other., O. Raška, K. Bernášková, I. Raška Jr., and Obsahuje seznam literatury
The aim of the study was to compare the bone mineral density (BMD) and body composition between ambulatory male MS patients and control subjects and to evaluate the relationships among body composition, motor disability, glucocorticoids (GC) use, and bone health. Body composition and BMD were measured by dual-energy X-ray absorptiometry in 104 ambulatory men with MS (mean age: 45.2 years) chronically treated with low-dose GC and in 54 healthy age-matched men. Compared to age-matched controls, MS patients had a significantly lower total body bone mineral content (TBBMC) and BMD at all measured sites except for the radius. Sixty five male MS patients (62.5 %) met the criteria for osteopenia and twenty six of them (25 %) for osteoporosis. The multivariate analysis showed a consistent dependence of bone measures (except whole body BMD) on BMI. The total leg lean mass % was as an independent predictor of TBBMC. The Expanded Disability Status Scale (EDSS), cumulative GC dose and age were independent determinants for BMD of the proximal femur. We conclude that decreasing mobility in male MS patients is associated with an increasing degree of osteoporosis and muscle wasting in the lower extremities. The chronic low-dose GC treatment further contributes to bone loss., V. Zikán ... [et al.]., and Obsahuje seznam literatury
The peak bone mass and the rate of bone loss are in part genetically determined. It has been suggested that bone mineral density (BMD) may be related to allelic variation in the apolipoprotein E (ApoE) gene locus. ApoE is important in the receptor-mediated clearance of chylomicron particles from the plasma, Apo E4 having the highest and Apo E2 the lowest receptor affinity. Chylomicrons are the main carrier of vitamin K in the plasma; vitamin K plays an important role in the carboxylation of osteocalcin. We have tested the hypothesis that persons with E4 variant would have lower BMD and increased bone turnover than those with E2 variant. A total of 18 ApoE 2/2 and ApoE 4/4 homozygotes were selected from 873 patients who were examined for the ApoE genotype. BMD in lumbar vertebral, femoral neck and distal forearm was measured and plasma concentrations of osteocalcin and C-terminal fragments of collagen (CTx) were determined. BMD values (expressed as T-score) at the three specified sites were -0.12± 1.72, -0.52± 1.32 and -0.52± 0.81 in ApoE 2/2 group and -0.24± 1.22, 0.00± 0.84 and -0.17± 1.07 in the ApoE 4/4 group. Plasma osteocalcin and CTx were within normal limits in both groups. In conclusion, we did not observe any association of ApoE genotype with BMD and biochemical markers of bone metabolism in ApoE 2/2 and ApoE 4/4 homozygotes., T. Štulc, R. Češka, A. Hořínek, J. Štěpán., and Obsahuje bibliografii
Exercise induced bone response although established, little is known about the molecular components that mediate bone response to mechanical loading (ML). In our recent QTL study, we identified one such possible molecular component responding to ML: cartilage oligomeric matrix protein (COMP). To address the COMP role in mediating ML effects on bone formation, COMP expression was evaluated as a function of duration and age in response to ML in female B6 mice. A 9N load was applied using a four-point bending device at 2Hz frequency for 36 cycles, once per day for 2-, 4- and 12-days on the right tibia. The left tibia was used as an internal control. Loading caused an increase in COMP expression by 1.3-, 2- and 4-fold respectively after 2-, 4- and 12-days of loading. This increase was also seen in 16 and 36-week old mice. Based on these findings, we next used COMP knockout (KO) mice to evaluate the cause and effect relationship. Quantitative analysis revealed 2 weeks of ML induced changes in vBMD and bone size in the KO mice (5.9 % and 21 % vs. unloaded bones) was not significantly different from control mice (7 % and 24 % vs. unloaded bones). Our results imply that COMP is not a key upstream mediator of the anabolic effects of ML on the skeleton., A. Sengul, S. Mohan, C. Kesavan., and Obsahuje seznam literatury
Bone is a target tissue for hormones, such as the sex steroids, parathormon, vitamin D, calcitonin, glucocorticoids, and thyroid hormones. In the last decade, other “non-classic” hormones that modulate the bone tissue have been identified. While incretins (GIP and GLP-1) inhibit bone remodeling, angiotensin acts to promote remodeling. Bone morphogenetic protein (BMP) has also been found to have anabolic effects on the skeleton by activating bone formation during embryonic development, as well as in the postnatal period of life. Bone has also been identified as an endocrine tissue that produces a number of hormones, that bind to and modulate extra-skeletal receptors. Osteocalcin occupies a central position in this context. It can increase insulin secretion, insulin sensitivity and regulate metabolism of fatty acids. Moreover, osteocalcin also influences phosphate metabolism via osteocyte-derived FGF23 (which targets the kidneys and parathyroid glands to control phosphate reabsorption and metabolism of vitamin D). Finally, osteocalcin stimulates testosterone synthesis in Leydig cells and thus may play some role in male fertility. Further studies are necessary to confirm clinically important roles for skeletal tissue in systemic regulations., I. Zofkova., and Obsahuje bibliografii
We investigated the renal response to direct renal nerve stimulation, 2 weeks following reversal of 24-h unilateral (left) ureteric obstruction. Renal nerve stimulation caused a 13-15 % fall in renal blood flow, in 4 groups of anesthetized rats following ureteric obstruction (n=9) or a sham operation (n=7) both with (n=9) and without (n=7) treatment with the mixed ETA/B receptor antagonist, bosentan. In the sham-operated rats, renal nerve stimulation did not change glomerular filtration rate but reduced urine flow rate (37±3 %, P<0.001), and absolute (38±4 %, P<0.001) and fractional (35±5 %, P<0.01) sodium excretion. Following unilateral ureteric obstruction, renal nerve stimulation increased glomerular filtration rate by 22±3 % (P<0.01), but reduced urine flow rate (14±2 %, P<0.001) and fractional sodium excretion (23±5 %, P<0.01). Bosentan treatment had no effect on baseline or renal responses to renal nerve stimulation in the sham group but normalized the renal response to renal nerve stimulation in the unilateral ureteric obstruction group. We conclude that 14 days after a 24-h period of unilateral ureteric obstruction there is an increase in GFR in response to direct renal nerve stimulation, which is due, in part, to the actions of endothelin at the time of obstruction., F. T. Hammad, A. M. Wheatley, G. Davis., and Obsahuje bibliografii
Our previous experiments revealed that water intoxication and osmotic BBB disruption in the rat allow penetration of high- molecular substances into the brain and that resulting changes in the internal environment of th e CNS lead to pathological development, such as the loss of integrity of myelin. The aim of the present study was to determine whether the previously described phenomena are associated with increased water content in the brain. To answer the question following methods were used: a) water intoxication : intraperitoneal administration of distilled water, b) osmotic BBB disruption: application of mannitol (20 %) selectively into the internal carotid artery, c) brain wet weight was measured after decapitation, and subsequently (after six days in thermostat set at 86 °C) the dry weight were estimated d) in animals with 20 % and 30 % hyperhydration the degree of myelin deterioration was estimated e) animal locomotor activity was tested by continuous behavior tracking and analysis. Brai n water content after water intoxication and following the administration of mannitol was higher than in the control group. Different degrees of hyperhydration led to different levels of brain water content and to different degrees of myelin impairment. Hyperhydration corresponding to 20 % of the body weight brought about lower locomotor activity. Increased water content in the brain after the BBB osmotic disruption is surprising because this method is frequently used in the clinical practice., P. Kozler, V. Riljak, J. Pokorný., and Obsahuje bibliografii a bibliografické odkazy
Functional magnetic resonance imaging (fMRI) was used to demonstrate the brain activation during volitional control of breathing in nine healthy human subjects. This type of breathing was induced by acoustic stimuli dictating the respiratory frequency. During the period of dictated breathing not only the frontal and temporal lobes of the brain, but also the parietal lobes were bilaterally activated. The frontal lobe was activated bilaterally in all subjects, with frequent activation of Brodmann areas 4 and 6. In the parietal lobe, activation could mostly be demonstrated in gyrus postcentralis and the same was true for area 22 in the temporal lobe., V. Šmejkal, R. Druga, J. Tintěra., and Obsahuje bibliografii
Over a century ago, hyperplasia and hypertrophy of astrocytes was noted as a histopathological hallmark of multiple sclerosis and was hypothesized to play an important role in the development and course of this disease. However until today, the factual contribution of astrocytes to multiple sclerosis is elusive. Astrocytes may play an active role during degeneration and demyelination by controlling local inflammation in the CNS, provoking damage of oligodendrocytes and axons, and glial scarring but might also be beneficial by creating a permissive environment for remyelination and oligodendrocyte precursor migration, proliferation, and differentiation. Recent findings from our lab suggest that brain lipid binding protein (FABP7) is implicated in the course of multiple sclerosis and the regulation of astrocyte function. The relevance of our findings and data from other groups are highlighted and discussed in this paper in the context of myelin repair., M. Kipp ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Our objective was to evaluate the utility of the natriuretic peptides BNP (brain natriuretic peptide) and NT-proBNP as markers of pulmonary artery systolic pressure (PASP) in trekkers ascending to high altitude (HA). 20 participants had BNP and NT- proBNP assayed and simultaneous echocardiographic assessment of PASP performed during a trek to 5150 m. PASP increased significantly (p=0.006) with ascent from 24±4 to 39±11 mm Hg at 5150 m. At 5150 m those with a PASP ≥ 40 mm Hg (n=8) (versus those with PASP<40 mm Hg) had higher post-exercise BNP (pg/ml): 54.5±36 vs. 13.4±17 (p=0.012). Their resting BNP at 5150 m was also higher: 57.3±43.4 vs. 12.6±13 (p=0.017). In those with a pathological ( ≥ 400 pg/ml) rise in NT-proBNP at 5150 m (n=4) PASP was significantly higher: 45.9±7.5 vs. 32.2±6.2 mm Hg (p=0.015). BNP and NT-proBNP may reflect elevated PASP, a central featur e of high altitude pulmonary oedema, at HA., D. R. Woods ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy